COVID-19-associated coagulopathy and acute kidney injury in critically ill patients.

OBJECTIVE: The incidence of thrombotic events and acute kidney injury is high in critically ill patients with COVID-19. We aimed to evaluate and compare the coagulation profiles of patients with COVID-19 developing acute kidney injury versus those who did not, during their intensive care unit stay. METHODS: Conventional coagulation and platelet function tests, fibrinolysis, endogenous inhibitors of coagulation tests, and rotational thromboelastometry were conducted on days 0, 1, 3, 7, and 14 following intensive care unit admission. RESULTS: Out of 30 patients included, 13 (43.4%) met the criteria for acute kidney injury. Comparing both groups, patients with acute kidney injury were older: 73 (60-84) versus 54 (47-64) years, p=0.027, and had a lower baseline glomerular filtration rate: 70 (51-81) versus 93 (83-106) mL/min/1.73m2, p=0.004. On day 1, D-dimer and fibrinogen levels were elevated but similar between groups: 1780 (1319-5517) versus 1794 (726-2324) ng/mL, p=0.145 and 608 (550-700) versus 642 (469-722) g/dL, p=0.95, respectively. Rotational thromboelastometry data were also similar between groups. However, antithrombin activity and protein C levels were lower in patients who developed acute kidney injury: 82 (75-92) versus 98 (90-116), p=0.028 and 70 (52-82) versus 88 (78-101) µ/mL, p=0.038, respectively. Mean protein C levels were lower in the group with acute kidney injury across multiple time points during their stay in the intensive care unit. CONCLUSION: Critically ill patients experiencing acute kidney injury exhibited lower endogenous anticoagulant levels. Further studies are needed to understand the role of natural anticoagulants in the pathophysiology of acute kidney injury within this population.

Impact of withholding early antibiotic therapy in nonseptic surgical patients with suspected nosocomial infection: a retrospective cohort analysis.

BACKGROUND: Systemic inflammatory responses mimicking infectious complications are often present in surgical patients. METHODS: The objective was to assess the association between withholding early antimicrobial therapy while investigating alternative diagnoses and worse outcomes in nonseptic patients with suspected nosocomial infection in a retrospective cohort of critically ill surgical patients. The initiation of antibiotic therapy within 24 h of the suspicion of infection was defined as the Early Empirical Antibiotic strategy (EEA) group and the initiation after 24 h of suspicion or not prescribed was defined as the Conservative Antibiotic strategy (CA) group. Primary outcome was composite: death, sepsis, or septic shock within 14 days. Main exclusion criteria were sepsis or an evident source of infection at inclusion. RESULTS: Three hundred and forty patients were eligible for inclusion (74% trauma patients). Age, sex, reason for hospital admission, SAPS3 score, SOFA score, and use of vasopressors or mechanical ventilation were not different between the groups. Within 14 days of inclusion, 100% (130/130) of EEA patients received antibiotics compared to 57% (120/210) of CA patients. After adjusting for confounding variables, there was no association between primary outcome and the groups. In a post hoc subgroup analysis including only patients with a posteriori confirmed infection (by microbiological cultures), delay in initiation of adequate antimicrobial therapy was independently associated with the primary outcome (Odds Ratio = 1.19 per day of delay; 95% CI 1.05-1.37). CONCLUSIONS: Withholding early empiric antibiotic therapy was not associated with progression of organ dysfunction within 14 days in nonseptic surgical patients with suspected nosocomial infection without an obvious source.

COVID-19-associated coagulopathy and acute kidney injury in critically ill patients

ABSTRACT Objective The incidence of thrombotic events and acute kidney injury is high in critically ill patients with COVID-19. We aimed to evaluate and compare the coagulation profiles of patients with COVID-19 developing acute kidney injury versus those who did not, during their intensive care unit stay. Methods Conventional coagulation and platelet function tests, fibrinolysis, endogenous inhibitors of coagulation tests, and rotational thromboelastometry were conducted on days 0, 1, 3, 7, and 14 following intensive care unit admission. Results Out of 30 patients included, 13 (43.4%) met the criteria for acute kidney injury. Comparing both groups, patients with acute kidney injury were older: 73 (60-84) versus 54 (47-64) years, p=0.027, and had a lower baseline glomerular filtration rate: 70 (51-81) versus 93 (83-106) mL/min/1.73m2, p=0.004. On day 1, D-dimer and fibrinogen levels were elevated but similar between groups: 1780 (1319-5517) versus 1794 (726-2324) ng/mL, p=0.145 and 608 (550-700) versus 642 (469-722) g/dL, p=0.95, respectively. Rotational thromboelastometry data were also similar between groups. However, antithrombin activity and protein C levels were lower in patients who developed acute kidney injury: 82 (75-92) versus 98 (90-116), p=0.028 and 70 (52-82) versus 88 (78-101) µ/mL, p=0.038, respectively. Mean protein C levels were lower in the group with acute kidney injury across multiple time points during their stay in the intensive care unit. Conclusion Critically ill patients experiencing acute kidney injury exhibited lower endogenous anticoagulant levels. Further studies are needed to understand the role of natural anticoagulants in the pathophysiology of acute kidney injury within this population.

Comparison of the accuracy of residents, senior physicians and surrogate decision-makers for predicting hospital mortality of critically ill patients. / Comparação da acurácia de residentes, médicos seniores e decisores substitutos na previsão da mortalidade hospitalar de pacientes críticos.

OBJECTIVE: To compare the predictive performance of residents, senior intensive care unit physicians and surrogates early during intensive care unit stays and to evaluate whether different presentations of prognostic data (probability of survival versus probability of death) influenced their performance. METHODS: We questioned surrogates and physicians in charge of critically ill patients during the first 48 hours of intensive care unit admission on the patient's probability of hospital outcome. The question framing (i.e., probability of survival versus probability of death during hospitalization) was randomized. To evaluate the predictive performance, we compared the areas under the ROC curves (AUCs) for hospital outcome between surrogates and physicians' categories. We also stratified the results according to randomized question framing. RESULTS: We interviewed surrogates and physicians on the hospital outcomes of 118 patients. The predictive performance of surrogate decisionmakers was significantly lower than that of physicians (AUC of 0.63 for surrogates, 0.82 for residents, 0.80 for intensive care unit fellows and 0.81 for intensive care unit senior physicians). There was no increase in predictive performance related to physicians' experience (i.e., senior physicians did not predict outcomes better than junior physicians). Surrogate decisionmakers worsened their prediction performance when they were asked about probability of death instead of probability of survival, but there was no difference for physicians. CONCLUSION: Different predictive performance was observed when comparing surrogate decision-makers and physicians, with no effect of experience on health care professionals' prediction. Question framing affected the predictive performance of surrogates but not of physicians.

OBJETIVO: Comparar o desempenho preditivo de residentes, médicos seniores de unidades de terapia intensiva e decisores substitutos dos pacientes logo no início da internação na unidade de terapia intensiva e avaliar se diferentes apresentações de prognóstico (probabilidade de sobrevida versus probabilidade de óbito) influenciaram seus desempenhos. MÉTODOS: Os decisores substitutos e os médicos responsáveis pelos pacientes críticos foram questionados durante as primeiras 48 horas de internação na unidade de terapia intensiva sobre a probabilidade do desfecho hospitalar do paciente. O enquadramento da pergunta (isto é, a probabilidade de sobrevida versus a probabilidade de óbito durante a internação) foi randomizado. Para avaliar o desempenho preditivo, comparou-se a área sob a curva ROC para desfecho hospitalar entre as categorias decisores substitutos e médicos. Também estratificaram-se os resultados de acordo com o enquadramento da pergunta randomizado. RESULTADOS: Entrevistaram-se decisores substitutos e médicos sobre os desfechos hospitalares de 118 pacientes. O desempenho preditivo dos decisores substitutos foi significativamente inferior ao dos médicos (área sob a curva de 0,63 para decisores substitutos, 0,82 para residentes, 0,80 para residentes de medicina intensiva e 0,81 para médicos seniores de unidade de terapia intensiva). Não houve aumento no desempenho preditivo quanto à experiência dos médicos (ou seja, médicos seniores não previram desfechos melhor que médicos juniores). Os decisores substitutos pioraram seu desempenho de previsão quando perguntados sobre a probabilidade de óbito ao invés da probabilidade de sobrevida, mas não houve diferença entre os médicos. CONCLUSÃO: Observou-se desempenho preditivo diferente ao comparar decisores substitutos e médicos, sem qualquer efeito da experiência no prognóstico dos profissionais de saúde. O enquadramento da pergunta afetou o desempenho preditivo dos substitutos, mas não o dos médicos.

Comparação da acurácia de residentes, médicos seniores e decisores substitutos na previsão da mortalidade hospitalar de pacientes críticos / Comparison of the accuracy of residents, senior physicians and surrogate decision-makers for predicting hospital mortality of critically ill patients

RESUMO Objetivo: Comparar o desempenho preditivo de residentes, médicos seniores de unidades de terapia intensiva e decisores substitutos dos pacientes logo no início da internação na unidade de terapia intensiva e avaliar se diferentes apresentações de prognóstico (probabilidade de sobrevida versus probabilidade de óbito) influenciaram seus desempenhos. Métodos: Os decisores substitutos e os médicos responsáveis pelos pacientes críticos foram questionados durante as primeiras 48 horas de internação na unidade de terapia intensiva sobre a probabilidade do desfecho hospitalar do paciente. O enquadramento da pergunta (isto é, a probabilidade de sobrevida versus a probabilidade de óbito durante a internação) foi randomizado. Para avaliar o desempenho preditivo, comparou-se a área sob a curva ROC para desfecho hospitalar entre as categorias decisores substitutos e médicos. Também estratificaram-se os resultados de acordo com o enquadramento da pergunta randomizado. Resultados: Entrevistaram-se decisores substitutos e médicos sobre os desfechos hospitalares de 118 pacientes. O desempenho preditivo dos decisores substitutos foi significativamente inferior ao dos médicos (área sob a curva de 0,63 para decisores substitutos, 0,82 para residentes, 0,80 para residentes de medicina intensiva e 0,81 para médicos seniores de unidade de terapia intensiva). Não houve aumento no desempenho preditivo quanto à experiência dos médicos (ou seja, médicos seniores não previram desfechos melhor que médicos juniores). Os decisores substitutos pioraram seu desempenho de previsão quando perguntados sobre a probabilidade de óbito ao invés da probabilidade de sobrevida, mas não houve diferença entre os médicos. Conclusão: Observou-se desempenho preditivo diferente ao comparar decisores substitutos e médicos, sem qualquer efeito da experiência no prognóstico dos profissionais de saúde. O enquadramento da pergunta afetou o desempenho preditivo dos substitutos, mas não o dos médicos.

ABSTRACT Objective: To compare the predictive performance of residents, senior intensive care unit physicians and surrogates early during intensive care unit stays and to evaluate whether different presentations of prognostic data (probability of survival versus probability of death) influenced their performance. Methods: We questioned surrogates and physicians in charge of critically ill patients during the first 48 hours of intensive care unit admission on the patient's probability of hospital outcome. The question framing (i.e., probability of survival versus probability of death during hospitalization) was randomized. To evaluate the predictive performance, we compared the areas under the ROC curves (AUCs) for hospital outcome between surrogates and physicians' categories. We also stratified the results according to randomized question framing. Results: We interviewed surrogates and physicians on the hospital outcomes of 118 patients. The predictive performance of surrogate decisionmakers was significantly lower than that of physicians (AUC of 0.63 for surrogates, 0.82 for residents, 0.80 for intensive care unit fellows and 0.81 for intensive care unit senior physicians). There was no increase in predictive performance related to physicians' experience (i.e., senior physicians did not predict outcomes better than junior physicians). Surrogate decisionmakers worsened their prediction performance when they were asked about probability of death instead of probability of survival, but there was no difference for physicians. Conclusion: Different predictive performance was observed when comparing surrogate decision-makers and physicians, with no effect of experience on health care professionals' prediction. Question framing affected the predictive performance of surrogates but not of physicians.

Coagulation profile of COVID-19 patients admitted to the ICU: An exploratory study.

BACKGROUND: Coagulation abnormalities in COVID-19 patients have not been addressed in depth. OBJECTIVE: To perform a longitudinal evaluation of coagulation profile of patients admitted to the ICU with COVID-19. METHODS: Conventional coagulation tests, rotational thromboelastometry (ROTEM), platelet function, fibrinolysis, antithrombin, protein C and S were measured at days 0, 1, 3, 7 and 14. Based on median total maximum SOFA score, patients were divided in two groups: SOFA ≤ 10 and SOFA > 10. RESULTS: Thirty patients were studied. Some conventional coagulation tests, as aPTT, PT and INR remained unchanged during the study period, while alterations on others coagulation laboratory tests were detected. Fibrinogen levels were increased in both groups. ROTEM maximum clot firmness increased in both groups from Day 0 to Day 14. Moreover, ROTEM-FIBTEM maximum clot firmness was high in both groups, with a slight decrease from day 0 to day 14 in group SOFA ≤ 10 and a slight increase during the same period in group SOFA > 10. Fibrinolysis was low and decreased over time in all groups, with the most pronounced decrease observed in INTEM maximum lysis in group SOFA > 10. Also, D-dimer plasma levels were higher than normal reference range in both groups and free protein S plasma levels were low in both groups at baseline and increased over time, Finally, patients in group SOFA > 10 had lower plasminogen levels and Protein C ​​than patients with SOFA <10, which may represent less fibrinolysis activity during a state of hypercoagulability. CONCLUSION: COVID-19 patients have a pronounced hypercoagulability state, characterized by impaired endogenous anticoagulation and decreased fibrinolysis. The magnitude of coagulation abnormalities seems to correlate with the severity of organ dysfunction. The hypercoagulability state of COVID-19 patients was not only detected by ROTEM but it much more complex, where changes were observed on the fibrinolytic and endogenous anticoagulation system.

Characteristics and outcomes of patients with COVID-19 admitted to the ICU in a university hospital in São Paulo, Brazil - study protocol.

OBJECTIVES: We designed a cohort study to describe characteristics and outcomes of patients with coronavirus disease (COVID-19) admitted to the intensive care unit (ICU) in the largest public hospital in Sao Paulo, Brazil, as Latin America becomes the epicenter of the pandemic. METHODS: This is the protocol for a study being conducted at an academic hospital in Brazil with 300 adult ICU beds dedicated to COVID-19 patients. We will include adult patients admitted to the ICU with suspected or confirmed COVID-19 during the study period. The main outcome is ICU survival at 28 days. Data will be collected prospectively and retrospectively by trained investigators from the hospital's electronic medical records, using an electronic data capture tool. We will collect data on demographics, comorbidities, severity of disease, and laboratorial test results at admission. Information on the need for advanced life support and ventilator parameters will be collected during ICU stay. Patients will be followed up for 28 days in the ICU and 60 days in the hospital. We will plot Kaplan-Meier curves to estimate ICU and hospital survival and perform survival analysis using the Cox proportional hazards model to identify the main risk factors for mortality. ClinicalTrials.gov: NCT04378582. RESULTS: We expect to include a large sample of patients with COVID-19 admitted to the ICU and to be able to provide data on admission characteristics, use of advanced life support, ICU survival at 28 days, and hospital survival at 60 days. CONCLUSIONS: This study will provide epidemiological data about critically ill patients with COVID-19 in Brazil, which could inform health policy and resource allocation in low- and middle-income countries.

Intensive support recommendations for critically-ill patients with suspected or confirmed COVID-19 infection.

In December 2019, a series of patients with severe pneumonia were identified in Wuhan, Hubei province, China, who progressed to severe acute respiratory syndrome and acute respiratory distress syndrome. Subsequently, COVID-19 was attributed to a new betacoronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Approximately 20% of patients diagnosed as COVID-19 develop severe forms of the disease, including acute hypoxemic respiratory failure, severe acute respiratory syndrome, acute respiratory distress syndrome and acute renal failure and require intensive care. There is no randomized controlled clinical trial addressing potential therapies for patients with confirmed COVID-19 infection at the time of publishing these treatment recommendations. Therefore, these recommendations are based predominantly on the opinion of experts (level C of recommendation).

Intensive support recommendations for critically-ill patients with suspected or confirmed COVID-19 infection / Recomendações de suporte intensivo para pacientes graves com infecção suspeita ou confirmada pela COVID-19

ABSTRACT In December 2019, a series of patients with severe pneumonia were identified in Wuhan, Hubei province, China, who progressed to severe acute respiratory syndrome and acute respiratory distress syndrome. Subsequently, COVID-19 was attributed to a new betacoronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Approximately 20% of patients diagnosed as COVID-19 develop severe forms of the disease, including acute hypoxemic respiratory failure, severe acute respiratory syndrome, acute respiratory distress syndrome and acute renal failure and require intensive care. There is no randomized controlled clinical trial addressing potential therapies for patients with confirmed COVID-19 infection at the time of publishing these treatment recommendations. Therefore, these recommendations are based predominantly on the opinion of experts (level C of recommendation).

RESUMO Em dezembro de 2019, uma série de pacientes com pneumonia grave foi identificada em Wuhan, província de Hubei, na China. Esses pacientes evoluíram para síndrome respiratória aguda grave e síndrome do desconforto respiratório agudo. Posteriormente, a COVID-19 foi atribuída a um novo betacoronavírus, o coronavírus da síndrome respiratória aguda grave 2 (SARS-CoV-2). Cerca de 20% dos pacientes com diagnóstico de COVID-19 desenvolvem formas graves da doença, incluindo insuficiência respiratória aguda hipoxêmica, síndrome respiratória aguda grave, síndrome do desconforto respiratório agudo e insuficiência renal aguda e requerem admissão em unidade de terapia intensiva. Não há nenhum ensaio clínico randomizado controlado que avalie potenciais tratamentos para pacientes com infecção confirmada pela COVID-19 no momento da publicação destas recomendações de tratamento. Dessa forma, essas recomendações são baseadas predominantemente na opinião de especialistas (grau de recomendação de nível C).

Characteristics and outcomes of patients with COVID-19 admitted to the ICU in a university hospital in São Paulo, Brazil - study protocol

OBJECTIVES: We designed a cohort study to describe characteristics and outcomes of patients with coronavirus disease (COVID-19) admitted to the intensive care unit (ICU) in the largest public hospital in Sao Paulo, Brazil, as Latin America becomes the epicenter of the pandemic. METHODS: This is the protocol for a study being conducted at an academic hospital in Brazil with 300 adult ICU beds dedicated to COVID-19 patients. We will include adult patients admitted to the ICU with suspected or confirmed COVID-19 during the study period. The main outcome is ICU survival at 28 days. Data will be collected prospectively and retrospectively by trained investigators from the hospital's electronic medical records, using an electronic data capture tool. We will collect data on demographics, comorbidities, severity of disease, and laboratorial test results at admission. Information on the need for advanced life support and ventilator parameters will be collected during ICU stay. Patients will be followed up for 28 days in the ICU and 60 days in the hospital. We will plot Kaplan-Meier curves to estimate ICU and hospital survival and perform survival analysis using the Cox proportional hazards model to identify the main risk factors for mortality. ClinicalTrials.gov: NCT04378582. RESULTS: We expect to include a large sample of patients with COVID-19 admitted to the ICU and to be able to provide data on admission characteristics, use of advanced life support, ICU survival at 28 days, and hospital survival at 60 days. CONCLUSIONS: This study will provide epidemiological data about critically ill patients with COVID-19 in Brazil, which could inform health policy and resource allocation in low- and middle-income countries.

Optimization of conditions for apnea testing in a hypoxemic brain dead patient. / Otimização de condições para teste de apneia em paciente hipoxêmico com morte encefálica.

We report the case of a patient in whom brain death was suspected and associated with atelectasis and moderate to severe hypoxemia even though the patient was subjected to protective ventilation, a closed tracheal suction system, positive end-expiratory pressure, and recruitment maneuvers. Faced with the failure to obtain an adequate partial pressure of oxygen for the apnea test, we elected to place the patient in a prone position, use higher positive end-expiratory pressure, perform a new recruitment maneuver, and ventilate with a higher tidal volume (8mL/kg) without exceeding the plateau pressure of 30cmH2O. The apnea test was performed with the patient in a prone position, with continuous positive airway pressure coupled with a T-piece. The delay in diagnosis was 10 hours, and organ donation was not possible due to circulatory arrest. This report demonstrates the difficulties in obtaining higher levels of the partial pressure of oxygen for the apnea test. The delays in the diagnosis of brain death and in the organ donation process are discussed, as well as potential strategies to optimize the partial pressure of oxygen to perform the apnea test according to the current recommendations.

Relatamos o caso de um paciente que evoluiu com suspeita de morte encefálica associada à atelectasia e à hipoxemia moderada a grave, apesar de instituídos ventilação protetora, sistema de aspiração traqueal fechado, pressão positiva ao final da expiração moderada e manobra de recrutamento. Diante da não obtenção de pressão parcial de oxigênio adequada para o teste de apneia, optamos por pronar o paciente, utilizar pressão positiva expiratória final mais elevada, realizar nova manobra de recrutamento e ventilar com volume corrente mais elevado (8mL/kg), sem ultrapassar pressão de platô de 30cmH2O. O teste de apneia foi realizado em posição prona, com válvula de pressão positiva contínua nas vias aéreas acoplada em tubo T. O atraso no diagnóstico foi de 10 horas; a doação de órgãos não foi possível devido à parada circulatória. Este relato demonstra as dificuldades para obtenção de níveis de pressão parcial de oxigênio mais altos para a realização do teste de apneia. Os atrasos que isso pode acarretar ao diagnóstico de morte encefálica e ao processo de doação de órgãos são discutidos, além de potenciais estratégias de otimização da pressão parcial de oxigênio para realização do teste, conforme as recomendações atuais.

Otimização de condições para teste de apneia em paciente hipoxêmico com morte encefálica / Optimization of conditions for apnea testing in a hypoxemic brain dead patient

RESUMO Relatamos o caso de um paciente que evoluiu com suspeita de morte encefálica associada à atelectasia e à hipoxemia moderada a grave, apesar de instituídos ventilação protetora, sistema de aspiração traqueal fechado, pressão positiva ao final da expiração moderada e manobra de recrutamento. Diante da não obtenção de pressão parcial de oxigênio adequada para o teste de apneia, optamos por pronar o paciente, utilizar pressão positiva expiratória final mais elevada, realizar nova manobra de recrutamento e ventilar com volume corrente mais elevado (8mL/kg), sem ultrapassar pressão de platô de 30cmH2O. O teste de apneia foi realizado em posição prona, com válvula de pressão positiva contínua nas vias aéreas acoplada em tubo T. O atraso no diagnóstico foi de 10 horas; a doação de órgãos não foi possível devido à parada circulatória. Este relato demonstra as dificuldades para obtenção de níveis de pressão parcial de oxigênio mais altos para a realização do teste de apneia. Os atrasos que isso pode acarretar ao diagnóstico de morte encefálica e ao processo de doação de órgãos são discutidos, além de potenciais estratégias de otimização da pressão parcial de oxigênio para realização do teste, conforme as recomendações atuais.

ABSTRACT We report the case of a patient in whom brain death was suspected and associated with atelectasis and moderate to severe hypoxemia even though the patient was subjected to protective ventilation, a closed tracheal suction system, positive end-expiratory pressure, and recruitment maneuvers. Faced with the failure to obtain an adequate partial pressure of oxygen for the apnea test, we elected to place the patient in a prone position, use higher positive end-expiratory pressure, perform a new recruitment maneuver, and ventilate with a higher tidal volume (8mL/kg) without exceeding the plateau pressure of 30cmH2O. The apnea test was performed with the patient in a prone position, with continuous positive airway pressure coupled with a T-piece. The delay in diagnosis was 10 hours, and organ donation was not possible due to circulatory arrest. This report demonstrates the difficulties in obtaining higher levels of the partial pressure of oxygen for the apnea test. The delays in the diagnosis of brain death and in the organ donation process are discussed, as well as potential strategies to optimize the partial pressure of oxygen to perform the apnea test according to the current recommendations.